Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ornithine decarboxylase (ODC) is the rate-limiting enzyme that catalyzes the synthesis of polyamines from ornithine and is thought to be involved in the cellular response to growth, differentiation, and stress. Previous studies have demonstrated that transient cerebral ischemia results in an increase in ODC activity and polyamine synthesis. We have used the Mongolian gerbil as a model system to test the hypothesis that the cellular response to ischemia induces a distinct pattern of ODC gene expression. Our results indicate that transient ischemia, induced by bilateral carotid occlusion, elevates ODC mRNA within 1-4 h after reperfusion, which correlates with increased ODC activity and polyamine synthesis. Increased ODC mRNA can be detected in the forebrain, striatum, hippocampus, and midbrain but not the cerebellum, which is not subject to ischemic injury. In contrast, c-fos mRNA increased by 15 min after reperfusion and actin mRNA did not demonstrate alterations in level after ischemia. Pentobarbital prevented the increase in ODC mRNA, whereas the glutamate antagonist MK-801 had no effect on the elevation of ODC gene expression after ischemia. We conclude that the ischemia-induced increase in ODC enzyme activity may be attributed in part to transcriptional activation of the ODC gene.
J Cereb Blood Flow Metab 1991 Nov
PMID:Modulation of ornithine decarboxylase mRNA following transient ischemia in the gerbil brain. 193 91

Reversible cerebral ischemia was produced in anesthetized Mongolian gerbils by occluding both common carotid arteries. After 5 min of ischemia, brains were recirculated for 8 or 24 h. Treated animals received a single intraperitoneal injection of pentobarbital (50 mg/kg) immediately after the aneurysm clips were removed. At the end of the experiments, animals were reanesthetized and their brains frozen in situ. Tissue samples were taken from the cerebral cortex, lateral striatum, CA1 subfield of the hippocampus, thalamus, and cerebellum for measuring ornithine decarboxylase (ODC) activity and putrescine levels. In addition, 20-microns-thick coronal tissue sections were taken from the level of the striatum and stained with hematoxylin/eosin for evaluating the extent of ischemic neuronal necrosis in the lateral striatum. In control animals ODC activity and putrescine levels amounted, respectively, to 0.32 +/- 0.03 nmol/g/h and 10.2 +/- 0.5 nmol/g in the cerebral cortex; 0.34 +/- 0.02 nmol/g/h and 12.8 +/- 0.5 nmol/g in the lateral striatum; 0.58 +/- 0.05 nmol/g/h and 10.5 +/- 0.7 nmol/g in the hippocampal CA1 subfield; 0.35 +/- 0.01 nmol/g/h and 9.8 +/- 0.4 nmol/g in the thalamus; and 0.25 +/- 0.01 nmol/g/h and 8.3 +/- 0.6 nmol/g in the cerebellum. After 5 min cerebral ischemia and 8 h recirculation, a significant 7- to 16-fold increase in ODC activity was observed in all forebrain structures studied. Following 24 h recirculation, ODC activity normalized in the cortex, striatum, and thalamus but was still significantly above control values in the hippocampal CA1 subfield.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1990 Mar
PMID:Ornithine decarboxylase activity and putrescine levels in reversible cerebral ischemia of Mongolian gerbils: effect of barbiturate. 230 40

Ornithine decarboxylase, rate-limiting in polyamine formation, has been found to be necessary for the development of vasogenic edema after cryogenic cerebral injury and is postulated to be of importance in late ischemic brain edema formation. Ornithine decarboxylase activity and accompanying edema was studied after transient cerebral ischemia in Mongolian gerbils. Bilateral carotid artery occlusion was utilized to produce dense forebrain ischemia. After 4 h of reperfusion a significant elevation in ornithine decarboxylase activity was present (72.5 +/- 24.7 vs 8.5 +/- 2 pmoles/mg protein/h, p less than 0.05). Immunohistochemical localization of ornithine decarboxylase indicated its presence in cortical neurons of ischemic gerbils. This was typically located in the perinuclear cytoplasm and extended into proximal dendrites. Nonischemic animals did not contain ornithine decarboxylase immunoreactivity. These studies show the presence and location of ornithine decarboxylase in cerebral tissue subjected to transient ischemia. The increase in this marker of polyamine activity paralleled previous studies in this model of cerebral edema formation and reperfusion deficit in blood flow and evoked potential, suggesting that ornithine decarboxylase is a marker for and may be associated with those late metabolic events leading to progressive functional deterioration after incomplete cerebral ischemia.
J Cereb Blood Flow Metab 1988 Dec
PMID:Ornithine decarboxylase activity and immunohistochemical location in postischemic brain. 319 49

1. A mutant of Saccharomyces cerevisiae, defective in ornithine decarboxylase, was isolated. A prolonged culture of the mutant in a polyamine-free medium resulted in a great decrease in the polyamine content and in cessation of growth. The addition of polyamines to the culture induced the growth after a lag period of 5--6.5 h. The growth rate in the presence of polyamine was comparable to that of the wild-type strain. The effectiveness of polyamines was as follows: spermidine greater than putrescine approximately equal to spermine. 2. Phosphatidylcholine-synthesizing activity during the lag phase of growth was determined by measuring the rate of incorporation of [14C]choline into phosphatidylcholine. The incorporation rate was markedly increased with time by polyamine prior to the initiation of cell division. Polyamines were effective in the following order: spermidine greater than putrescine approximately equal to spermine. Experiments with methylglyoxal bis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, showed that putrescine stimulates cell growth and choline incorporation into phosphatidylcholine after it has been converted into spermidine in the cell. 3. The induction of the choline transport system was shown to be responsible for the increase in the rate of incorporation of [14C]choline into phosphatidylcholine effected by polyamines. A low concentration of cycloheximide completely prevented the induction of choline transport by polyamines. The levels of the CDP-choline pathway enzymes such as choline kinase, cholinephosphate cytidyltransferase and cholinephosphotransferase were not significantly changed.
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PMID:Induction of choline transport and its role in the stimulation of the incorporation of choline into phosphatidylcholine by polyamines in a polyamine auxotroph of Saccharomyces cerevisiae. 701

Polyamines are derived from ornithine by the actions of ornithine decarboxylase (ODC), which is the rate-limiting step in this pathway. Polyamines play a role in cell growth, neoplasia, differentiation, and response to injury. We have shown that transient cerebral ischemia gives rise to increased ODC mRNA and enzyme activity in the gerbil brain. ODC and polyamines are thought to be important in the generation of edema and the neuronal cell loss associated with cerebral ischemia. To test this theory, we examined the ODC activity, putrescine levels, and neuronal density in the CA1 region of the hippocampus following ischemia and reperfusion injury in the absence and presence of an inhibitor of ODC activity, alpha-difluoromethylornithine (DFMO). Pretreatment of animals with DFMO resulted in attenuation of the ODC activity following 5 min of ischemia and 4 h of reperfusion. In addition, DFMO prevented the increase in polyamine levels, as determined by measurement of putrescine in the ischemic brain. These alterations were not due to changes in ODC mRNA level. Further analysis revealed that DFMO treatment blocked the delayed neuronal cell death in the CA1 region of the hippocampus that accompanies ischemia and reperfusion injury. Administration of DFMO resulted in a dose-dependent beneficial effect upon neuronal cell survival. These results suggest that ODC enzyme activity and the production of polyamines play a significant role in the response of the brain to ischemic injury.
J Cereb Blood Flow Metab 1994 Nov
PMID:Blockade of ornithine decarboxylase enzyme protects against ischemic brain damage. 792 46

Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is induced in ischemic tissue and may mediate vasogenic edema and delayed neuronal death. We determined the effects of alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC, on infarct size and ODC activity in a rat model of transient focal ischemia. DFMO blocked the ischemia-induced increase in ODC and significantly reduced infarct volumes by 57-45%, depending upon the treatment regimen. These studies suggest that polyamine metabolism plays a role in the development of cerebral infarction after focal ischemia and that DFMO may be useful in limiting injury after a stroke.
J Cereb Blood Flow Metab 1993 Nov
PMID:DFMO reduces cortical infarct volume after middle cerebral artery occlusion in the rat. 840 13

Transient cerebral ischemia leads to increased expression of ornithine decarboxylase (ODC). Contradicting studies attributed neuroprotective and neurotoxic roles to ODC after ischemia. Using antisense oligonucleotides (ODNs), the current study evaluated the functional role of ODC in the process of neuronal damage after transient focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats. Transient MCAO significantly increased the ODC immunoreactive protein levels and catalytic activity in the ipsilateral cortex, which were completely prevented by the infusion of antisense ODN specific for ODC. Transient MCAO in rats infused with ODC antisense ODN increased the infarct volume, motor deficits, and mortality compared with the sense or random ODN-infused controls. Results of the current study support a neuroprotective or recovery role, or both, for ODC after transient focal ischemia.
J Cereb Blood Flow Metab 2001 Aug
PMID:Ornithine decarboxylase knockdown exacerbates transient focal cerebral ischemia-induced neuronal damage in rat brain. 1148 30